Clinical presentation and initial management of black men and white men with prostate cancer in the United Kingdom: the PROCESS cohort study.

BACKGROUND: In the United States, Black men have a higher risk of prostate cancer and worse survival than do White men, but it is unclear whether this is because of differences in diagnosis and management. We re-examined these differences in the United Kingdom, where health care is free and unlikely to vary by socioeconomic status. METHODS: This study is a population-based retrospective cohort study of men diagnosed with prostate cancer with data on ethnicity, prognostic factors, and clinical care. A Delphi panel considered the appropriateness of investigations and treatments received. RESULTS: At diagnosis, Black men had similar clinical stage and Gleason scores but higher age-adjusted prostate-specific antigen levels (geometric mean ratio 1.41, 95% confidence interval (95% CI): 1.15-1.73). Black men underwent more investigations and were more likely to undergo radical treatment, although this was largely explained by their younger age. Even after age adjustment, Black men were more likely to undergo a bone scan (odds ratio 1.37, 95% CI: 1.05-1.80). The Delphi analysis did not suggest differential management by ethnicity. CONCLUSIONS: This UK-based study comparing Black men with White men found no evidence of differences in disease characteristics at the time of prostate cancer diagnosis, nor of under-investigation or under-treatment in Black men.

Pathways to diagnosis for Black men and White men found to have prostate cancer: the PROCESS cohort study.

Black men in England have three times the age-adjusted incidence of diagnosed prostate cancer as compared with their White counterparts. This population-based retrospective cohort study is the first UK-based investigation of whether access to diagnostic services underlies the association between race and prostate cancer. Prostate cancer was ascertained using multiple sources including hospital records. Race and factors that may influence prostate cancer diagnosis were assessed by questionnaire and hospital records review. We found that Black men were diagnosed an average of 5.1 years younger as compared with White men (P<0.001). Men of both races were comparable in their knowledge of prostate cancer, in the delays reported before presentation, and in their experience of co-morbidity and symptoms. Black men were more likely to be referred for diagnostic investigation by a hospital department (P=0.013), although general practitioners referred the large majority of men. Prostate-specific antigen levels were comparable at diagnosis, although Black men had higher levels when compared with same-age White men (P<0.001). In conclusion, we found no evidence of Black men having poorer access to diagnostic services. Differences in the run-up to diagnosis are modest and seem insufficient to explain the higher rate of prostate cancer diagnosis in Black men.

Detection of human chorionic gonadotrophin-beta in serum or urine of prostate cancer patients is of no clinical significance.

The aim of this study was to prospectively evaluate the potential role of elevated urinary/serum human chorionic gonadotrophin-beta (hCGbeta) in prostate cancer prognosis. 104 patients with newly diagnosed prostate cancers were included; 68 patients had organ-confined, 18 had locally advanced and 18 had metastatic disease. A control group consisted of 115 patients presenting with benign prostatic disease. Serum and urinary total hCGbeta was measured prior to treatment and serum PSA was measured at diagnosis. The patients were treated along conventional lines and progression-free survival was assessed. Four patients had elevated serum and 10 had elevated urinary, total hCGbeta. There were no significant correlations between serum/urinary levels of hCGbeta and tumour stage, Gleason score or PSA. In contrast, serum PSA had significant linear correlations with both clinical tumour stage and Gleason score (p = 0.0001). At a median follow-up of 36 months, 22 (21.2%) patients had died while 17 (16.3%) others had progressed. Kaplan-Meier plots and log-rank test revealed no significant difference in progression-free survival between patients with elevated or normal levels of serum and/or urinary total hCGbeta. Clinical tumour stage, grade and PSA were statistically significant prognostic variables. Immunoassay measurement of serum or urinary hCGbeta has no significant role in the clinical management of prostate cancer.

Evidence of an association between use of anti-microbial agents in food animals and anti-microbial resistance among bacteria isolated from humans and the human health consequences of such resistance.

Several lines of evidence indicate that the use of anti-microbial agents in food animals is associated with anti-microbial resistance among bacteria isolated from humans. The use of anti-microbial agents in food animals is most clearly associated with anti-microbial resistance among Salmonella and Campylobacter isolated from humans, but also appears likely among enterococci, Escherichia coli and other bacteria. Evidence is also accumulating that the anti-microbial resistance among bacteria isolated from humans could be the result of using anti-microbial agents in food animals and is leading to human health consequences. These human health consequences include: (i) infections that would not have otherwise occurred and (ii) increased frequency of treatment failures and increased severity of infection. Increased severity of infection includes longer duration of illness, increased frequency of bloodstream infections, increased hospitalization and increased mortality. Continued work and research efforts will provide more evidence to explain the connection between the use of anti-microbial agents in food animals and anti-microbial-resistant infections in humans. One particular focus, which would solidify this connection, is to understand the factors that dictate spread of resistance determinants, especially resistant genes. With continued efforts on the part of the medical, veterinary and public health community, such research may contribute to more precise guidelines on the use of anti-microbials in food animals.

Prediction of progression in pTa and pT1 bladder carcinomas with p53, p16 and pRb.

Currently available prognostic tools appear unable to adequately predict recurrence and progression in non muscle-invasive bladder carcinomas. We aimed to assess the prognostic value of immunohistochemical evaluation of the cell cycle markers p53, p16 and pRb. Paraffin blocks were obtained from 78 cases of pTa and pT1 transitional cell carcinomas, for which long-term follow-up was available. Representative sections were stained using antibodies against p53, p16 and pRb. Altered marker expression was found in 45, 17 and 30% of cases, respectively. Concurrent alteration of two or three markers occurred in 19% of cases, and was significantly associated with grade and stage. In univariate survival analysis, the concurrent alteration of any two markers was significantly associated with progression. The greatest risk was produced by alteration of both p53 and p16, which increased the risk of progression by 14.45 times (95% confidence interval (CI) 3.10-67.35). After adjusting for grade and stage, this risk was 7.73 (CI 1.13-52.70). The markers did not generally predict tumour recurrence, except in the 25 pT1 tumours. In these, p16 alteration was associated with a univariate risk of 2.83 (CI 1.01-7.91), and concurrent p53 and p16 alteration with a risk of 9.29 (CI 1.24-69.50). Overall, we conclude that the immunohistochemical evaluation of p53 and p16 may have independent prognostic value for disease progression, and may help guide management decisions in these tumours.

Testis conserving chemotherapy in germ cell cancer: its potential to increase understanding of the biology and treatment of carcinoma-in-situ.

Prompted by recognition of the potential of chemotherapy to increase the success of testis conserving surgery in patients with germ cell cancer, background and outcome data are reviewed and their contribution to the ongoing debate about how germ cell cancer develops discussed. The review is based on three previous studies of: a) time trends in tumour size in 578 personal series of all stages of testis cancer treated since 1978; b) impact of chemotherapy on actuarial risk of tumours in contralateral testis examined on 1221 patients treated in trials through the Anglian Germ Cell Cancer Consortium; and c) testes conservation attempted using chemotherapy in 78 patients. Since 1978 tumour size has decreased from 4.8 to 3.0 cms while cure has gone from 77 to 97%. There was no overall long term reduction in second cancers beyond 10 years in stage 1 patients after orchidectomy alone compared to stage 1 or metastatic disease patients receiving chemotherapy though the incidence was non significantly lower up to 10 years particularly in those patients receiving etoposide based combination. Testis conservation was initially successful in 28 of 78 (36%). An additional 25 (32%) had no viable cancer in orchidectomy specimen. In the 28 primary tumours cured by chemotherapy there was a 26% late relapse rate between 5 and 10 years (all cured by orchidectomy) compared to less than 5% in those cured with established metastases. In conclusion, testis conservation with chemotherapy is safe and feasible, though relapse is too frequent for routine service use. Confirmation of the high frequency of late relapse by others has raised the question whether these recurrences are due to post pubertal events reinducing CIS in intrauterine oestrogen primed germ cells and highlights the potential of testes conservation studies to better understand germ cell cancer development.

Phase 1/2 study of synchronous methotrexate, cisplatin, vincristine (MOPq10) chemotherapy and radiation for patients with locally advanced bladder cancer.

PURPOSE: This phase 1/2 study was designed to test toxicity and effectiveness of combination chemotherapy and concurrent radiotherapy in the treatment of invasive bladder cancer. METHODS AND MATERIALS: 17 patients with localised muscle-invasive bladder cancer, clinical stages T2-3 N0, M0, were treated with a radiotherapy schedule of 55 Gy in 20 fractions over 4 weeks restricted to the bladder and 3 cycles of concurrent dose-intensive combination chemotherapy consisting of cisplatin 60 mg/m(2), vincristine 2 mg and methotrexate 60 mg/m(2) at 10-day intervals (MOPq10). RESULTS: The complete remission rate following MOPq10 chemotherapy and radiotherapy was 88% as assessed at first cystoscopy with 82% remaining disease-free at 1 year. Risk factor analysis shows those older than 63 years (median) and those with creatinine clearance equal or less than the mean did worse. Actuarial disease-free survival at 2 years was 68% and of the patients treated 4/17 experienced acute G3/4 toxicity. CONCLUSION: This combination regimen was feasible. Its high initial response rate justifies further exploration in a randomised phase 2/3 trial setting with bladder volume and quality of life assessment.

Testicular microlithiasis: is it a benign condition with malignant potential?

OBJECTIVE: To review the findings of testicular ultrasonography (US) in patients referred for testicular symptoms including pain, swelling and infertility, and to determine the prevalence of testicular microlithiasis (TM) and ist relevance to the development of testicular cancer. METHODS: Records of 3,026 patients referred for testicular US between 1994 and 1999 were evaluated. The indications for testicular US diagnosis, management and relevant histological details were obtained from medical records. Patients with TM had an annual sonographic follow-up unless they had testicular cancer, in which case follow-up repeat US with clinical reviews was more frequent. RESULTS: TM was found in 54 patients (1.77%; median age 34 years, range 12-83 years). The median follow-up was 36 months (range 12-18 months). Sixteen of these patients had testicular malignancy (30%). The remaining 38 patients had hydrocele and epididymal cysts (14), varicocele (7), epididymitis (2) and small testes (8), with 14 patients having no other pathology. One patient with a small testis developed a seminoma while under surveillance. Another patient with metastatic embryonal-cell carcinoma at initial diagnosis was found to have a seminoma 4 years following chemotherapy. The relative risk of testicular tumours in the presence of TM was 13.2 (confidence interval 8.3-21.5). CONCLUSION: TM can no longer be regarded simply as a benign condition because of its association with testicular malignancy. In our series, 2 patients (5.2%) developed interval testicular cancers during follow-up US. There is no convincing evidence to suggest that TM might be premalignant. In rare instances of radiologically indeterminate cases, biopsy of the testis may be necessary.

Emergency sperm extraction for transient erectile dysfunction prior to assisted conception.

PURPOSE: During assisted conception treatment the male partner is under stress and consequently can fail to produce semen sample prior to egg collection. Failure to produce spermatozoa at a given time could lead to cancellation of the procedure. METHODS: We report the use of emergency percutaneous epididymal sperm aspiration (PESA) for temporary erectile dysfunction in a couple undergoing in vitro fertilization treatment. In the last 2 years, we saw three men who failed to produce a semen sample on the day of their partners' egg collection procedure. RESULTS: In the first case the male partner failed to produce semen after egg collection and the cycle was canceled. This clinical scenario was likely to recur and one of the options was to consider PESA. In the second case the male partner was counseled about the availability of PESA but he managed to produce spermatozoa at home. The third patient was unable to produce a semen sample despite being provided audiovisual support and being allowed to go home. Five hours after the egg collection, emergency PESA was performed after appropriate counseling. The procedure yielded motile spermatozoa which were used for intracytoplasmic sperm injection which resulted in successful fertilization, embryo transfer, and pregnancy. CONCLUSIONS: This case emphasizes that surgical procedures, such as PESA,TESA, and TESE, are useful alternatives but should be the last option to obtain sperm for ART. Other nonsurgical procedures, such as audiovisual aids, producing sperm at home, and the use of sildenafil citrate (Viagra) must be offered first to men with temporary erectile dysfunction during ART treatment.

Haematuria: a long-term problem after prostatectomy.

OBJECTIVE: The causes of 'late' haematuria (2 years or more) following endoscopic and open prostatectomy were studied. METHODS: Between 1994 and 1996, more than 400 patients were evaluated for haematuria. Ninety patients with post-prostatectomy haematuria were investigated with upper tract imaging and cystoscopic examination. Amongst these 90 patients, 30 presented with haematuria within 2 years of surgery. These patients were excluded from the study as they had normal investigations. RESULTS: Of these 60 patients, 24 (43%) had demonstrable causes of haematuria in their urinary tract. Six of them had urinary tract malignancy. CONCLUSIONS: There is a substantial likelihood of finding a cause for haematuria in patients who had prostatectomy even though they had full-scale urological investigations before. There is a need, therefore, to carry out necessary screening investigations in such patients.

Low dose aspirin as prophylaxis against renal-vein thrombosis in renal-transplant recipients.

BACKGROUND: Renal-vein thrombosis (RVT) is an infrequent event that accounts for a high proportion of early renal allograft losses, since graft failure secondary to acute irreversible rejection is now relatively rare. The cause of RVT may be related to technical problems, clotting disorders, diabetes, or cyclosporin, but is often difficult to define. METHODS: This retrospective study was performed to examine the influence of aspirin on the incidence of RVT in cadaveric and living-related renal transplant recipients receiving cyclosporin-based triple immunosuppression. The Oxford Transplant Centre database was used to identify all early (<30 day) non-immunological graft failures and case histories were examined for clinical and pathological evidence of RVT. In July 1991, aspirin (75 mg o.d. starting immediately before and continuing for 1 month post-transplant) was introduced as routine prophylaxis against RVT. Prior to this, aspirin prophylaxis was not used. RESULTS: In the 6-year period from July 1985 to June 1991, there were 27 cases of RVT in 475 transplants (5.6%). In the subsequent 6-year period, there were six cases of RVT in 480 transplants (1.2%) (P:<0.01). CONCLUSION: Although not abolished, this indicates a significant reduction in the incidence of RVT with the addition of low-dose aspirin.

Imaging with prostate-specific membrane antigen (PSMA) in prostate cancer.

Radioimmunoscintigraphy using a radio-labelled antibody to prostate-specific membrane antigen (PSMA) has growing applications as a means of tissue-specific imaging based on functional characteristics and complements traditional staging investigations. Clinical applications in men with carcinoma of the prostate are being refined, and this study reports outcomes with this technique in our practice. Prostatic immunoscintigraphy scans were performed with In-111 CYT 356 in 49 men with carcinoma of the prostate, obtaining sequential images in two and three dimensions at 10 min, 24 and 48 h. Of the 49 men, 36 had clinically localized cancer, 10 had recurrent disease after radical radiotherapy or radical prostatectomy and three had rising PSA after primary endocrine treatment. Scan findings are discussed in the context of clinical management. Of the 36 men with clinically localized cancer, seven had increased uptake in regional and distant lymph nodes. Of these seven, three were treated with hormone manipulation, two by radical prostatectomy and two by radical radiotherapy. Among 10 patients who had recurrence after radical treatment of the primary tumour, scans showed local recurrence alone in four, and six had regional or distant metastases. Three patients treated with primary hormone manipulation had scans for rising PSA, and of these one had a positive regional node and two had distant soft tissue and bone metastases. In conclusion, prostatic radio-immunoscintigraphy scans highlight tissues involved by prostate cancer, including the prostate, lymph nodes, soft tissues and bone metastases as well as pelvic recurrence. Results may contribute to the clinical management of individual patients, although histological confirmation may be appropriate when considering alternative treatment. Prostate Cancer and Prostatic Diseases (2000) 3, 47-52